Butt, J. H. et al. (2023) Urinary cGMP (cyclic guanosine monophosphate)/BNP (B-type natriuretic peptide) ratio, sacubitril/valsartan, and outcomes in heart failure with reduced ejection fraction: an analysis of the PARADIGM-HF trial. Circulation: Heart Failure, 16(3), pp. 247-258. (doi: 10.1161/CIRCHEARTFAILURE.122.010111) (PMID:36943907) (PMCID:PMC10022671)
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Abstract
Background: The ratio of ucGMP (urinary cyclic guanosine monophosphate) to BNP (B-type natriuretic peptide) is thought to reflect the responsiveness of tissues to natriuretic peptides. Methods: We examined the relationship between ucGMP/BNP ratio and clinical outcomes, the effect of sacubitril/valsartan, compared with enalapril, on the ucGMP/BNP ratio, and the efficacy of sacubitril/valsartan on clinical outcomes according to baseline ucGMP/BNP ratio in PARADIGM-HF trial (Prospective Comparison of ARNI With ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure). ucGMP/BNP ratio was available at baseline (N=2031), 1 month (N=1959), and 8 months after randomization (N=1746). The primary outcome was a composite of heart failure hospitalization or cardiovascular death. Results: Compared with the lowest tertile of baseline ucGMP/BNP ratio, patients in the higher tertiles had a lower risk of the primary outcome (tertile 1, reference; tertile 2, hazard ratio 0.57 [95% CI, 0.45–0.71]; tertile 3, hazard ratio, 0.54 [0.43–0.67]). Compared with baseline, the ucGMP/BNP ratio at 1 month and 8 months after randomization was higher with sacubitril/valsartan than with enalapril: ratio of geometric mean ratios at 1 month, 1.38 (95% CI, 1.27–1.51) and 8 months, 1.32 (95% CI, 1.20–1.45), and this difference was consistent across tertiles of ucGMP/BNP ratio at baseline (Pinteraction=0.19 and 0.91, respectively). The effect of sacubitril/valsartan, compared with enalapril, was consistent across tertiles of ucGMP/BNP ratio at baseline for all outcomes (Pinteraction ≥0.31). Conclusions: In patients with heart failure and reduced ejection fraction, higher ucGMP/BNP ratio was associated with better outcomes. Sacubitril/valsartan increased the ucGMP/BNP ratio, compared with enalapril, and the effect of sacubitril/valsartan on clinical outcomes was not modified by baseline ucGMP/BNP ratio. Registration: URL: https://www.clinicaltrials.gov; Unique Identifier: NCT01035255.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Butt, Mr Jawad and Jhund, Professor Pardeep and Dewan, Dr Pooja and McMurray, Professor John and Kober, Professor Lars |
| Authors: | Butt, J. H., Ibrahim, W., Dewan, P., Desai, A. S., Køber, L., Prescott, M. F., Lefkowitz, M. P., Rouleau, J. L., Solomon, S. D., Zile, M. R., Packer, M., Jhund, P. S., and McMurray, J. J.V. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health |
| Journal Name: | Circulation: Heart Failure |
| Publisher: | American Heart Association |
| ISSN: | 1941-3289 |
| ISSN (Online): | 1941-3297 |
| Published Online: | 25 January 2023 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Circulation: Heart Failure 16(3): 247-258 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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